The Effect of Chrysin Loaded PLGA-PEG on Metalloproteinase Gene Expression in Mouse 4T1 Tumor Model

Drug Res (Stuttg). 2017 Apr;67(4):211-216. doi: 10.1055/s-0042-122136. Epub 2017 Feb 6.


Despite the advances in medicine, cancer remains as one of the leading causes of the death worldwide. Through our previous study, the Chrysin loaded PGLA/PEG has been synthesized, and its physico-chemical properties were characterized. The aim of the present study was to evaluate the Chrysin loaded PGLA/PEG nanoparticle therapeutic effects on TIMP-1, TIMP-2, MMP-2, MMP-9 and PI3k expression in Mouse 4T1 breast tumor model.30 mice were enrolled in the current study, and the mice were randomly divided into 3 groups: untreated (n=10), Chrysin treatment (n=10) and Chrysin-loaded PLGA/PEG-based treatment (n=10). 1064T1 mammary carcinoma cells subcutaneously inoculated in the flank on mice orthotopically. After the treatments, the primary tumors were isolated from the Mice under anesthesia. For RNA extraction, the isolated tissues were frozen in -70°C. RNA extraction was performed by using RNA extraction kit. The expression of TIMP-1, TIMP-2, MMP-2 and MMP-9 were measured by the real time PCR.The study results showed the expression of TIMP-1 and TIMP-2 in Chrysin-loaded PLGA/PEG treatment groups was higher than Chrysin receiving one. Also, the results showed that the MMP-9 and MMP-2 expressions were reduced after Chrysin loaded PLGA/PEG treatment. The reduction of the mentioned genes was greater in Chrysin-loaded PLGA/PEG treatment group in comparison with Chrysin receiving group.According to our present study, expression of the mentioned genes after treatments, Chrysin; especially, Chrysin-loaded PLGA/PEG could be proposed as a new component in the cancer therapy for reducing the progression and metastasis.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Carriers / chemistry
  • Female
  • Flavonoids / administration & dosage
  • Flavonoids / therapeutic use*
  • Humans
  • Lactic Acid / chemistry*
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Nanoparticles / chemistry
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism


  • Antineoplastic Agents
  • Drug Carriers
  • Flavonoids
  • Timp1 protein, mouse
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • chrysin
  • Phosphatidylinositol 3-Kinases
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse